Domains of physical activity and all-cause mortality: systematic review and dose-response meta-analysis of cohort studies

Background The dose-response relation between physical activity and all-cause mortality is not well defined at present. We conducted a systematic review and meta-analysis to determine the association with all-cause mortality of different domains of physical activity and of defined increases in physical activity and energy expenditure. Methods MEDLINE, Embase and the Cochrane Library were searched up to September 2010 for cohort studies examining all-cause mortality across different domains and levels of physical activity in adult general populations. We estimated combined risk ratios (RRs) associated with defined increments and recommended levels, using random-effects meta-analysis and dose-response meta-regression models. Results Data from 80 studies with 1 338 143 participants (118 121 deaths) were included. Combined RRs comparing highest with lowest activity levels were 0.65 [95% confidence interval (95% CI) 0.60-0.71] for total activity, 0.74 (95% CI 0.70-0.77) for leisure activity, 0.64 (95% CI 0.55-0.75) for activities of daily living and 0.83 (95% CI 0.71-0.97) for occupational activity. RRs per 1-h increment per week were 0.91 (95% CI 0.87-0.94) for vigorous exercise and 0.96 (95% CI 0.93-0.98) for moderate-intensity activities of daily living. RRs corresponding to 150 and 300 min/week of moderate to vigorous activity were 0.86 (95% CI 0.80-0.92) and 0.74 (95% CI 0.65-0.85), respectively. Mortality reductions were more pronounced in women. Conclusion Higher levels of total and domain-specific physical activity were associated with reduced all-cause mortality. Risk reduction per unit of time increase was largest for vigorous exercise. Moderate-intensity activities of daily living were to a lesser extent beneficial in reducing mortalit

Regulation of Cx45 hemichannels mediated by extracellular and intracellular calcium

Connexin45 (Cx45) hemichannels (HCs) open in the absence of Ca2+ and close in its presence. To elucidate the underlying mechanisms, we examined the role of extra- and intracellular Ca2+ on the electrical properties of HCs. Experiments were performed on HeLa cells expressing Cx45 using electrical (voltage clamp) and optical (Ca2+ imaging) methods. HCs exhibit a time- and voltage-dependent current (I hc), activating with depolarization and inactivating with hyperpolarization. Elevation of [Ca2+]o from 20nM to 2μM reversibly decreases I hc, decelerates its rate of activation, and accelerates its deactivation. Our data suggest that [Ca2+]o modifies the channel properties by adhering to anionic sites in the channel lumen and/or its outer vestibule. In this way, it blocks the channel pore and reversibly lowers I hc and modifies its kinetics. Rapid lowering of [Ca2+]o from 2mM to 20nM, achieved early during a depolarizing pulse, led to an outward I hc that developed with virtually no delay and grew exponentially in time paralleled by unaffected [Ca2+]i. A step increase of [Ca2+]i evoked by photorelease of Ca2+ early during a depolarizing pulse led to a transient decrease of I hc superimposed on a growing outward I hc; a step decrease of [Ca2+]i elicited by photoactivation of a Ca2+ scavenger provoked a transient increase in I hc. Hence, it is tempting to assume that Ca2+ exerts a direct effect on Cx45 hemichannel

Dual mode of action of IP3-dependent SR-Ca2+ release on local and global SR-Ca2+ release in ventricular cardiomyocytes.

In heart muscle, the physiological function of IP3-induced Ca2+ release (IP3ICR) from the sarcoplasmic reticulum (SR) is still the subject of intense study. A role of IP3ICR may reside in modulating Ca2+-dependent cardiac arrhythmogenicity. Here we observe the propensity of spontaneous intracellular Ca2+ waves (SCaW) driven by Ca2+-induced Ca2+ release (CICR) in ventricular myocytes as a correlate of arrhythmogenicity on the organ level. We observe a dual mode of action of IP3ICR on SCaW generation in an IP3R overexpression model. This model shows a mild cardiac phenotype and mimics pathophysiological conditions of increased IP3R activity. In this model, IP3ICR was able to increase or decrease the occurrence of SCaW depending on global Ca2+ activity. This IP3ICR-based regulatory mechanism can operate in two "modes" depending on the intracellular CICR activity and efficiency (e.g. SCaW and/or local Ryanodine Receptor (RyR) Ca2+ release events, respectively): a) in a mode that augments the CICR mechanism at the cellular level, resulting in improved excitation-contraction coupling (ECC) and ultimately better contraction of the myocardium, and b) in a protective mode in which the CICR activity is curtailed to prevent the occurrence of Ca2+ waves at the cellular level and thus reduce the probability of arrhythmogenicity at the organ level

Morphable Face Models - An Open Framework

In this paper, we present a novel open-source pipeline for face registration based on Gaussian processes as well as an application to face image analysis. Non-rigid registration of faces is significant for many applications in computer vision, such as the construction of 3D Morphable face models (3DMMs). Gaussian Process Morphable Models (GPMMs) unify a variety of non-rigid deformation models with B-splines and PCA models as examples. GPMM separate problem specific requirements from the registration algorithm by incorporating domain-specific adaptions as a prior model. The novelties of this paper are the following: (i) We present a strategy and modeling technique for face registration that considers symmetry, multi-scale and spatially-varying details. The registration is applied to neutral faces and facial expressions. (ii) We release an open-source software framework for registration and model-building, demonstrated on the publicly available BU3D-FE database. The released pipeline also contains an implementation of an Analysis-by-Synthesis model adaption of 2D face images, tested on the Multi-PIE and LFW database. This enables the community to reproduce, evaluate and compare the individual steps of registration to model-building and 3D/2D model fitting. (iii) Along with the framework release, we publish a new version of the Basel Face Model (BFM-2017) with an improved age distribution and an additional facial expression model

Calcium waves driven by "sensitization” wave-fronts

Objective: Cellular Ca2+ waves are understood as reaction-diffusion systems sustained by Ca2+-induced Ca2+ release (CICR) from Ca2+ stores. Given the recently discovered sensitization of Ca2+ release channels (ryanodine receptors; RyRs) of the sarcoplasmic reticulum (SR) by luminal SR Ca2+, waves could also be driven by RyR sensitization, mediated by SR overloading via Ca2+ pump (SERCA), acting in tandem with CICR. Methods: Confocal imaging of the Ca2+ indicator fluo-3 was combined with UV-flash photolysis of caged compounds and the whole-cell configuration of the patch clamp technique to carry out these experiments in isolated guinea pig ventricular cardiomyocytes. Results: Upon sudden slowing of the SERCA in cardiomyocytes with a photoreleased inhibitor, waves indeed decelerated immediately. No secondary changes of Ca2+ signaling or SR Ca2+ content due to SERCA inhibition were observed in the short time-frame of these experiments. Conclusions: Our findings are consistent with Ca2+ loading resulting in a zone of RyR ‘sensitization' traveling within the SR, but inconsistent with CICR as the predominant mechanism driving the Ca2+ waves. This alternative mode of RyR activation is essential to fully conceptualize cardiac arrhythmias triggered by spontaneous Ca2+ releas

Medical use of cannabis in Switzerland: analysis of approved exceptional licences

In recent years, the Swiss Federal Office of Public Health (FOPH) granted exceptional licenses for the medical use of cannabinoids, typically for 6 months with possible extensions. A systematic review of cannabinoids for medical use commissioned by the FOPH supports the use of cannabinoids for the treatment of chronic pain and spasticity. However, little is known about the patients treated with cannabinoids. We aimed to study medical uses of cannabinoids as part of the FOPH's programme of exceptional licenses.; We examined all requests for medical use of cannabinoids sent to FOPH in 2013 and 2014. A standardised data sheet was developed to extract data from the files of approved requests. We extracted the duration of the licence, the year it was granted, and the payer of the therapy. At the level of the patient we collected the date of birth, sex, region of residence, diagnosis and the indication. Ethical approval was granted by the Ethics Committee of the Canton of Bern.; We analysed 1193 patients licenced for cannabinoid treatment in 2013 or 2014. During 2013, 542 patients were treated under the exceptional licencing programme (332 requesting physicians) compared with 825 in 2014 (446 physicians). Over half of patients (685; 57%) were women. The mean age was 57 years (standard deviation 15.0), chronic pain (49%) and spasticity (40%) were the most common symptoms, and co-medication was reported for 39% of patients. Seventy-eight different diagnoses were recorded, including multiple sclerosis (257 patients, 22%), soft tissue disorders (119, 10%), dorsalgia (97, 8.1%), spinal muscular atrophy (65, 5.5%) and paraplegia/tetraplegia (62, 5.2%). Licence extensions were granted to 143 patients (26.4%) in 2013 and 324 patients (39.3%) in 2014. There were substantial regional variations of the rates of patients treated with cannabinoids. On average, eight patients per 100 000 residents received an exceptional licence. Most patients (1083, 91%) paid out of pocket.; Exceptional licences for medical use of cannabinoids have increased substantially in Switzerland, with the programme including patients with a wide range of conditions

High life in the sky? Mortality by floor of residence in Switzerland

Living in high-rise buildings could influence the health of residents. Previous studies focused on structural features of high-rise buildings or characteristics of their neighbourhoods, ignoring differences within buildings in socio-economic position or health outcomes. We examined mortality by floor of residence in the Swiss National Cohort, a longitudinal study based on the linkage of December 2000 census with mortality and emigration records 2001-2008. Analyses were based on 1.5 million people living in buildings with four or more floors and 142,390 deaths recorded during 11.4 million person-years of follow-up. Cox models were adjusted for age, sex, civil status, nationality, language, religion, education, professional status, type of household and crowding. The rent per m2 increased with higher floors and the number of persons per room decreased. Mortality rates decreased with increasing floors: hazard ratios comparing the ground floor with the eighth floor and above were 1.22 [95% confidence interval (CI) 1.15-1.28] for all causes, 1.40 (95% CI 1.11-1.77) for respiratory diseases, 1.35 (95% CI 1.22-1.49) for cardiovascular diseases and 1.22 (95% CI 0.99-1.50) for lung cancer, but 0.41 (95% CI 0.17-0.98) for suicide by jumping from a high place. There was no association with suicide by any means (hazard ratio 0.81; 95% CI 0.57-1.15). We conclude that in Switzerland all-cause and cause-specific mortality varies across floors of residence among people living in high-rise buildings. Gradients in mortality suggest that floor of residence captures residual socioeconomic stratification and is likely to be mediated by behavioural (e.g. physical activity), and environmental exposures, and access to a method of suicid